This invention pertains generally to the field of phantoms for use with medical imaging such as ultrasound scanning, magnetic resonance imaging and computed tomography.
There has been a tremendous surge in the number of ultrasound guided transperineal prostate implants performed in recent years. Effective implants require involved treatment planning based on three-dimensional multi-modality (magnetic resonance imaging, ultrasound, computed tomography) images used in combination with one another. A multi-modality prostate imaging phantom could have applications in quality assurance, image registration and treatment planning. Three human soft tissues relevant to a prostate phantom that should be mimicked for magnetic resonance imaging (MRI), ultrasound, and computed tomography (CT) are prostate parenchyma, skeletal muscle and adipose (fat) tissue.
Tissue-mimicking (TM) materials must exhibit the same properties relevant to a particular imaging modality as actual human soft tissues. Tissue-mimicking materials for use in magnetic resonance imaging phantoms should have values of characteristic relaxation times, T1 and T2, which correspond to those of the tissue represented at the Larmor frequency of concern. Soft tissues exhibit T1 values ranging from about 200-1200 ms and T2 values from about 40-200 ms. For a given soft tissue, T1 in particular can exhibit a significant dependence on frequency as well as on temperature. However, for multi-modality imaging phantoms, in general, measurements may be performed near the available clinical Larmor frequency of an MRI system (typically 64 MHz or 85 MHz) and at room temperature. Phantoms must be assumed to be useful at room temperature even though their properties must mimic those of soft tissues at the normal body temperature of 37xc2x0 C.
The ideal tissue-mimicking material for use in ultrasound should have the same ranges of speeds of sound, attenuation coefficients, and backscatter coefficients as soft tissue. These parameters should be controllable in the manufacturing process of the phantom material, and their variation within the range of room temperatures should be small. Speeds of sound in human soft tissues vary over a fairly small range with an average value of about 1540 m/s. The speed of sound in fat is thought to be about 1470 m/s. The amplitude attenuation coefficients appear to vary over the range from 0.4 dB/cm to about 2 dB/cm at a frequency of 1 MHz in these tissues. The frequency dependencies of the attenuation coefficient of some soft tissues have been studied and, typically, it has been reported that the attenuation coefficient is approximately proportional to the ultrasonic frequency in the diagnostic frequency range of 1 to 10 MHz. An exception is breast fat, in which the attenuation coefficient is proportional to the frequency to the 1.7 power. F. T. D""Astous and F. S. Foster, xe2x80x9cFrequency Dependence of Attenuation and Backscatter in Breast Tissue,xe2x80x9d Ultrasound in Med. and Biol., Vol. 12, pp. 795-808 (1986).
For use in computed tomography (CT), the tissue-mimicking materials must exhibit the same CT number as that of the tissue being mimicked. The CT numbers for most soft tissues lie in the range of about 20-70 at the typical effective x-ray energy of a clinical CT scanner except for fat where the CT number is about xe2x88x92100.
In addition to the individual imaging modality parameters listed above, tissue-mimicking materials must also exhibit long term stability and ease of storage without which they are rendered useless in an imaging phantom.
An ultrasound phantom containing tissue-mimicking material is disclosed in U.S. Pat. No. 4,277,367, to Madsen, et al., entitled Phantom Material and Methods, in which both the speed of sound and the ultrasonic attenuation properties could be simultaneously controlled in a mimicking material based on water based gels, such as those derived from animal hides. In one embodiment, ultrasound phantoms embodying the desired features for mimicking soft tissue were prepared from a mixture of gelatin, water, n-propanol and graphite powder, with a preservative. In another embodiment, an oil and gelatin mixture formed the basis of the tissue-mimicking material.
Tissue-mimicking material is typically used to form the body of an ultrasound scanner phantom. This is accomplished by enclosing the material in a container which is closed by an ultrasound transmitting window cover. The tissue-mimicking material is admitted to the container in such a way as to exclude air bubbles from forming in the container. Tissue-mimicking materials may contain scattering particles, spaced sufficiently close to each other that an ultrasound scanner is incapable of resolving individual scattering particles. Testing spheres of tissue-mimicking material, or other targets, may be located within the phantom container, suspended in the tissue-mimicking material body. The objective is for the ultrasound scanner to resolve the testing spheres or other targets from the background material and scattering particles. This type of ultrasound phantom is described in U.S. Pat. No. 4,843,866, to Madsen, et al., entitled Ultrasound Phantom.
U.S. Pat. No. 5,625,137 to Madsen, et al. discloses a tissue-mimicking material for ultrasound phantoms with very low acoustic backscatter coefficient that may be in liquid or solid form. A component in both the liquid and solid forms is a filtered aqueous mixture of large organic water soluble molecules and an emulsion of fatty acid esters, which may be based on a combination of milk and water. Hydroxy compounds, such as n-propanol, can be used to control the ultrasonic speed of propagation through the material and a preservative from bacterial invasion can also be included. The use of scattering particles allows a very broad range of relative backscatter levels to be achieved.
Hydrogen magnetic resonance imaging (MRI) (also known as nuclear magnetic resonance, or NMR, imaging) is generally a more complicated imaging procedure than X-ray or ultrasound since it does not measure just one dominant property, such as electron density in the case of X-ray computed tomography, but is affected by the hydrogen atom density, flow, and two relaxation phenomena. The contrast, or differences in image brightness, in an MRI image is primarily due to differences in the relaxation times of tissues. It has been found that there are relaxation time differences between normal tissue and certain tumors, which makes MRI imaging potentially very valuable in early detection of such tumors.
A satisfactory MRI phantom must satisfy several requirements. First, the material of which the phantom is made should mimic the hydrogen density and relaxation times of several types of tissues. Second, the relaxation times of the material should not change over time, such as over several months or years, so that the phantom can be used in tests of imager reproducibility. Third, if the phantom includes inclusions of materials within the surrounding matrix which have different NMR characteristics than the surrounding matrix, these inclusions must be stable over time in both shape and in NMR relaxation times, T1 and T2.
Soft tissues exhibit T2""s from about 40 ms to 200 ms. Typical values for the ratio T1/T2 lie between 4 and 10 for soft tissues. For a given soft tissue parenchyma, T1 in particular can exhibit a significant dependence on frequency as well as temperature.
Materials which have been proposed for use in phantoms to mimic soft tissues with respect to one or more NMR properties include aqueous solutions of paramagnetic salts and water based gels of various forms. Such gels may also contain additives such as a paramagnetic salt for control of T1. Aqueous solutions of paramagnetic salts can be used in phantoms to produce a desired value of either T1 or T2. The ratio of T1/T2 in the salt solutions is almost always less than 2, however, rendering such solutions inadequate for the close mimicking of soft tissue, with the possible exception of body fluids.
Phantom materials composed of water based agar gels doped with MnCl2 to control T1 have been reported. R. Mathur-DeVre, et al., xe2x80x9cThe Use of Agar as a Basic Reference for Calibrating Relaxation Times and Imaging Parameters,xe2x80x9d Magn. Reson. Med., Vol. 2, 1985, p. 176. Agar gels doped with CuSO4 have also been reported. M. D. Mitchell, et al., xe2x80x9cAgarose as a Tissue-Equivalent Phantom Material for NMR Imaging,xe2x80x9d Magn. Reson. Imag., Vol. 4, 1986, p. 263.
A phantom material consisting of mixtures of agar gel and animal hide gel in which CuSO4 was used to lower T1 has also been reported. Unfortunately, a long-term instability manifested itself in that a steady, very slow rise in T1 was observed over a period of months. This instability precludes the use of this material in MRI phantoms. The rise in T1 was perhaps due to the slow formation of metal-organic complexes, removing the Cu++ paramagnetic ions. J. C. Blechinger, et al., xe2x80x9cNMR Properties for Tissue-Like Gel Mixtures for Use as Reference Standards or in Phantoms,xe2x80x9d Med. Phys., Vol. 12, 1985, p. 516 (Abstract).
More recently, the problem of gradual increase in T1 in the agar, animal hide gel, Cu++SO4xe2x88x92xe2x88x92 gel has been eliminated by addition of the chelating agent EDTA (ethylenediaminetetraacetic acid). This stable material is excellent for use in MRI phantoms. See J. R. Rice, et al., xe2x80x9cAnthropomorphic 1H MRS Head Phantom,xe2x80x9d Medical Physics, Vol. 25, 1998, pp. 1145-1156.
U.S. Pat. No. 5,312,755 to Madsen et al. discloses a tissue-mimicking NMR phantom that utilizes a base tissue-mimicking material which is a gel solidified from a mixture of animal hide gelatin, agar, water and glycerol. The amount of glycerol could be used to control the T1. The preferred base material included a mixture of agar, animal hide gelatin, distilled water (preferably deionized), glycerol, n-propyl alcohol, formaldehyde, and p-methylbenzoic acid. The contrast resolution phantom could include inclusions which have NMR properties which differ from the base tissue-mimicking material. Differences in contrast between the surrounding base material and the spherical inclusions could also be obtained by the use of a solid such as powdered nylon added to the base material and the inclusions that has little NMR response but displaces some of the gelatin solution, decreasing the apparent 1H density to the NMR instrument.
As noted above, phantoms for use in MRI systems made from water-based agarose gels along with a copper salt have been made previously. M. D. Mitchell, et al., supra. The T1 and T2 relaxation rates are strongly dependent on the concentrations of agarose and copper ions in the tissue-mimicking sample with the T1 depending more on the copper and the T2 depending more strongly on the concentration of dry weight agarose in the sample. Burlew et al. xe2x80x9cA New Ultrasound Tissue-Equivalent Material,xe2x80x9d Radiology, Vol. 134, 1980, pp. 517-520, have described a polysaccharide gel (agar) for ultrasound phantoms that can be made to exhibit speeds of sound over the range of 1498 m/s to 1600 m/s at 22xc2x0 C.
A prostate phantom based on CT slices and made from solid water (Gammex/RMI, Madison, Wis.) for imaging, volume rendering, treatment planning, and dosimetry applications has also been constructed. B. B. Paliwal, et al., xe2x80x9cA Solid Water Pelvic and Prostate Phantom for Imaging, Volume Rendering, Treatment Planning, and Dosimetry for an RTOG Multi-Institutional, 3-D Dose Escalation Study,xe2x80x9d International Journal of Radiation Oncology, Biology, Physics, Vol. 42, 1998, pp. 205-211.
An earlier investigation had reported on whether tissue-mimicking (TM) materials for ultrasound might be appropriate for use in magnetic resonance imaging (MRI) phantoms as well. See, E. L. Madsen, et al., xe2x80x9cProspective Tissue-mimicking Material For Use In NMR Imaging Phantoms,xe2x80x9d Magn. Reson. Imaging, Vol. 1, 1982, pp. 135-141. These materials consisted of powdered graphite and preservatives in water-based proteinaceaous gels. Though the materials looked promising initially, later measurements revealed that, although T1 was mimicked adequately, it was the T2* which was being controlled through concentration of graphite, not T2 itself. For tissue-mimicking materials, it is the T2 which must be controlled because T2 is intrinsic to the material whereas T2* is influenced by the involved imager instrumentation.
In accordance with the invention, a tissue-mimicking material is provided for imaging phantoms that can be used with two or more types of imaging modalities, such as ultrasound scanning, magnetic resonance imaging, and computed tomography. The tissue-mimicking material may be adjusted to appropriately mimic human tissue in the several modes of imaging for particular tissues such as organs, skeletal muscle, and fat. The materials mimicking the various tissues may be incorporated in direct contact with one another in an imaging phantom and remain stable in their multi-modal imaging properties over time, allowing such phantoms to be used for long-term calibration and evaluation of the imaging instruments. Phantoms in accordance with the invention have particular application in simulating prostate tissue which is surrounded by and adjacent to muscle and fat tissue.
Each component material in a tissue-mimicking material influences ultrasound, CT and MRI properties to a greater or lesser extent. There is at least one combination that yields good representation of the essential properties for all three modalities for that tissue-mimicking material (e.g., prostate parenchyma). In addition, different tissue-mimicking materials should be capable of remaining in direct contact without changes in their ultrasound, CT and MRI properties for long periods of timexe2x80x94months or yearsxe2x80x94to allow construction of anthropomorphic phantoms without the need for unrealistic image-degrading diffusion barrier between tissue-mimicking materials.
A preferred multi-imaging modality tissue-mimicking material for use in phantoms with at least ultrasound and MRI comprises an aqueous mixture of large organic water soluble molecules, a copper salt, a chelating agent for binding the copper ions in the salt, a gel-forming material, and glass or plastic beads intermixed therewith to provide a selected ultrasound attenuation coefficient, the glass or plastic beads selected and treated to have a low effect on the MRI T1 and T2 properties of the tissue-mimicking material. Such a material is particularly suitable for mimicking skeletal muscle tissue in both MRI and ultrasound imaging. A preferred gel-forming material is agarose, a preferred copper salt is CuCl2, and the large organic water soluble molecules are preferable derived from condensed milk. EDTA may be utilized as the chelating agent. The glass beads are utilized to adjust the ultrasound attenuation coefficient of the material to the desired level but have no substantial effect on MRI properties. The glass beads may be treated, such as by soaking in nitric acid to clean the surfaces thereof, to reduce the effect of any surface contamination on the glass beads on MRI properties.
An imaging phantom for use with at least ultrasound and MRI in accordance with the invention includes a phantom container and a tissue-mimicking material within the container, the tissue-mimicking material comprising at least two distinct sections in contact with each other, the tissue-mimicking material in the at least two sections in contact with each other including an aqueous mixture of large organic water soluble molecules, a copper salt, a chelating agent for binding the copper ions in the salt, and a gel-forming material, and wherein one of the sections includes glass beads intermixed therewith to provide a selected ultrasound attenuation coefficient to mimic muscle tissue, the glass beads treated to have a low effect on the MRI properties of the tissue-mimicking material. A section in contact with that section has glass beads or a larger size organ tissues such as prostate. The tissue-mimicking material may comprise at least two distinct sections in contact with each other, the two sections having first, small diameter glass or plastic beads (less than 20 xcexcm diameter) intermixed therewith to provide a selected ultrasound attenuation coefficient, and wherein one of the sections includes larger beads (greater than 30 xcexcm mean diameter) intermixed therewith to provide a selected backscatter coefficient therein. A preferred gel-forming agent is agar, and the dry weight concentration of agar in the section having glass beads therein is preferably higher than the dry weight concentration in the adjacent section to mimic the MRI properties of muscle tissue. A further section mimicking fat may also be in contact with one or both of the sections mimicking muscle tissue and organ tissue. Fat tissue may be mimicked by various materials including liquid vegetable oils such as safflower oil. In a region for mimicking fat, an open-cell reticulated mesh material that holds oil, such as the polyurethane material used in air filters, can be employed, with the liquid vegetable oil filling the interstices within the polyurethane material. Such a structure provides realistic ultrasound backscatter, simulating that due to the connective tissue matrix in real adipose tissue.
Further objects, features and advantages of the invention will be apparent from the following detailed description when taken in conjunction with the accompanying drawings.